thymus transplantation with immunosuppression

Conditions: DiGeorge Syndrome; DiGeorge Anomaly; Complete DiGeorge Anomaly; Complete DiGeorge Syndrome

Summary: the research purpose is to determine if thymus transplantation with immunosuppression is a safe and effective treatment for complete digeorge anomaly. the research includes studies to evaluate whether thymus transplantation results in complete digeorge anomaly subjects developing a normal immune system.

digeorge anomaly is a complex of cardiac defects, parathyroid deficiency, and thymus absence, resulting in profound t-cell deficiency. there is a spectrum of disease in digeorge anomaly with respect to all three defects. for complete digeorge anomaly subjects with severe t cell defect, the pi had shown that thymus transplantation is safe and efficacious without pretransplantation immunosuppression and with pretransplantation thymoglobulin and cyclosporine. some digeorge patients have very poor t cell function and are at risk of death from infection or other immune problems; however, these patients have enough t cell function to reject grafts. this protocol was designed for these patients. atypical phenotype and some typical phenotype digeorge subjects were included in this protocol. atypical complete digeorge anomaly patients have rash, lymphadenopathy, and oligoclonal t cell proliferations. the t cells have no markers of thymic function (they do not co-express cd45ra and cd62l; they do not contain t cell receptor rearrangement excision circles, trecs). typical complete digeorge anomaly patients in this protocol are those whose pha response \>20 fold. although these patients have very low t cell function, it may be enough to reject a transplant, so thymoglobulin was used.

Eligibility criteria:
transplant inclusion * no age limit * thyroid studies must be done and if abnormal, must be on therapy digeorge diagnosis - must have 1 symptom from the following list: * heart defect * hypocalcemia requiring replacement * 22q11 hemizygosity * 10p13 hemizygosity * charge association * abnormal ears plus mother with diabetes (type i, type ii, or gestational) atypical diagnosis: * must have, or have had, a rash. if rash present, biopsy of rash must show t cells in skin. if rash \& adenopathy resolved, must still have oligoclonal t cells. * within 1 month of tx must have pha response \>20 fold above background or \>5,000 cpm, whichever is higher, or response can be \< this. * circulating cd3+ t cells \>50/mm3 but cd45ra+cd62l+cd3+ t cells \<50/mm or \<5% of cd3 count, whichever is higher (must be done 2x) * immunoscope with \>40% oligoclonal tcrbv families. a 2nd test per sponsor discretion if t cell numbers increase or activation status changes. * if trec done pre-tx must have trecs \<100 per 100,000 cd3+ cells. typical diagnosis: * circulating cd3+ cd45ra+ cd62l+ t cells and \<50/mm3 or \<5% of total t cells * pha response \>20 fold above background or \>5,000 cpm, whichever is higher. * 2 studies must show similar immunological findings qualify for this study. * trecs, if done, should be \<100/100,000 cd3 cells transplant exclusion: * heart surgery \<4 weeks pre-tx date * heart surgery anticipated w/in 3 months of proposed tx * rejection by surgeon or anesthesiologist as surgical candidates * lack of sufficient muscle tissue to accept 0.2 grams/kg transplant

Keywords: thymus transplantation digeorge anomaly digeorge syndrome athymia low t cell numbers immunoreconstitution immunodeficiency complete digeorge typical digeorge atypical digeorge complete digeorge anomaly